New　Delhi　metallo-beta-lactamase-1　(NDM-1)　has　emerged　as　a　major　global　threat　to　human　health　for　its　rapid　rate　of　dissemination　and　ability　to　make　pathogenic　microbes　resistant　to　almost　all　known　beta-lactam　antibiotics.　In　addition,　effective　NDM-1　inhibitors　have　not　been　identified　to　date.　In　spite　of　the　plethora　of　structural　and　kinetic　data　available,　the　accurate　molecular　characteristics　of　and　details　on　the　enzymatic　reaction　of　NDM-1　hydrolyzing　beta-lactam　antibiotics　remain　incompletely　understood.　In　this　study,　a　combined　computational　approach　including　molecular　docking,　molecular　dynamics　simulations　and　quantum　mechanics/molecular　mechanics　calculations　was　performed　to　characterize　the　catalytic　mechanism　of　meropenem　catalyzed　by　NDM-1.　The　quantum　mechanics/molecular　mechanics　results　indicate　that　the　ionized　D124　is　beneficial　to　the　cleavage　of　the　C-N　bond　within　the　beta-lactam　ring.　Meanwhile,　it　is　energetically　favorable　to　form　an　intermediate　if　no　water　molecule　coordinates　to　Zn2.　Moreover,　according　to　the　molecular　dynamics　results,　the　conserved　residue　K211　plays　a　pivotal　role　in　substrate　binding　and　catalysis,　which　is　quite　consistent　with　previous　mutagenesis　data.　Our　study　provides　detailed　insights　into　the　catalytic　mechanism　of　NDM-1　hydrolyzing　meropenem　beta-lactam　antibiotics　and　offers　clues　for　the　discovery　of　new　antibiotics　against　NDM-1　positive　strains　in　clinical　studies.